Interferons belong to the family of cytokines which are cell-secreted proteins that typically act on target cells via specific plasma membrane receptors present on the surface of the target cells. A common feature of these receptors is the presence of an internal sequence of hydrophobic amino acids forming the transmembranal(TM) domain, which anchors the receptor in the outer membrane of the cell (Bazan, J. F., Proc. Natl. Acad. Sci. USA 87 6934-6938 (1990)). A human type I IFN receptor, designated IFN .alpha.-receptor protein (IFNAR) was characterized by cloning of its cDNA (Uze, G., and Gresser, I., Cell 60, 225-234 (1990)). This cDNA encodes an IFNAR protein having a 21 amino acid-long hydrophobic transmembranal region, which separates an N-terminal extracellular (EC) domain of 436 amino acids, from a C-terminal intracellular (IC) domain of 100 amino acids (see FIG. 1, scheme 1). It has been shown that the EC domain is involved in ligand binding (Benoit, P., et al., J. Immunol. 150, 707-716 (1993); Novick, D., et al., FEBS letters 314, 445-448 (1992)).
The existence of soluble non-membrane bound forms of receptors has been recognized (Fernandez-Botran, R., FASEB Journal 5, 2567-2574 (1991)). Such receptors are often formed by a proteolytic cleavage which occurs between the extracellular domain and the transmembranal region, thereby resulting in the shedding of a truncated receptor (Nophar, Y., et al., EMBO J.9, 3269-3278 (1990); Mullberg, J., et al., Eur. J. Immunol. 23, 473-480 (1993). Moreover, cells have also been found to synthesize other forms of cytokine receptors lacking the transmembranal and intracellular domains, which are, however, not as a result of proteolytic cleavage, but due to a differential processing of the receptor gene transcripts (Raines, M. A. et al., Proc. Natl. Acad. Sci. USA, 88, 8203-8207 (1991); Lust, J. A. et al., Cytokine 4, 96-100 (1992)). These non-transmembranal or "soluble" forms are characterized by a novel amino acid sequence at the C-terminus, making them distinct proteins, with probably distinct functions. Heretofore, non-transmembranal or "soluble" IFN .alpha.-receptors have not been described.